H2TPP Organocatalysis in Mild and Highly Regioselective Ring Opening of Epoxides to Halo Alcohols by Means of Halogen Elements
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Molecules 2012, 17, 5508-5519; doi:10.3390/molecules17055508 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Article H2TPP Organocatalysis in Mild and Highly Regioselective Ring Opening of Epoxides to Halo Alcohols by Means of Halogen Elements Parviz Torabi 1,*, Javad Azizian 2 and Shahab Zomorodbakhsh 1 1 Department of Chemistry, Mahshahr Branch, Islamic Azad University, Mahshahr 63519, Iran 2 Department of Chemistry, Faculty of Science, Science and Research Branch, Islamic Azad University, Tehran 11365, Iran * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +98-652-232-7070; Fax: +98-652-233-8586. Received: 10 January 2012; in revised form: 6 April 2012 / Accepted: 12 April 2012 / Published: 9 May 2012 Abstract: We found that elemental iodine and bromine are converted to trihalide nucleophiles (triiodine and tribromide anion, respectively) in the presence of catalytic amounts of meso-tetraphenylporphyrins (H2TPP). Therefore a highly regioselective method for the synthesis of -haloalcohols through direct ring opening of epoxides with elemental iodine and bromine in the presence of H2TPPs as new catalysts is described. At room temperature a series of epoxide derivatives were converted into the corresponding halohydrins resulting from an attack of trihalide species anion atoms at the less substituted carbon atom. This method occurs under neutral and mild conditions with high yields in various aprotic solvents, even when sensitive functional groups are present. Keywords: oxirane; ring opening; nucleophilic addition; elemental halogen; meso-tetraarylporphyrine; halohydrine 1. Introduction Oxiranes are among the most versatile intermediates in organic synthesis, as they can be easily prepared from a variety of other functional groups [1] and due to their ring strain and high reactivity, their reactions with various nucleophiles lead to highly regio and stereoselective ring opened products [2–4]. Vicinal halohydrins have found wide applications in organic transformations and in the Molecules 2012, 17 5509 synthesis of marine natural products [5,6]. The availability of some epoxides in an optically active form has enhanced their use as synthetic intermediates; a reaction sequence allows an impressive access to a large variety of compounds in an optically active form [7,8]. However, their direct conversion to halohydrins remains a reaction of considerable interest [9]. A variety of reagents are known to convert epoxides to halohydrins; the ring openings of unsymmetrically substituted epoxides with Li2(NiBr4) [10], LiX-(Bmim)PF6 [11], haloborane reagents [12], Br2/PPh3 [13], SmI2 [14], Ti(O-i-pr)4 [15], chlorosilanes [16], Lewis acids [3,17,18] and BF3-Et2O [19] have been reported. In particular metal halides such as Li/Ti [2], Sn [20], P [13], Cu [21], and Ni [10] easily induce epoxide-opening, in which the use of a stronger Lewis acid and a metal ion in structure of catalyst often results in low yields of the halohydrins when other sensitive functional groups are present [22]. However, in these approaches we encountered with some limitations, such as the need for strong Lewis acid and protic media that certainly are unsuitable conditions for complex epoxide compounds. Recently, it has been found that epoxides can be converted into iodoalcohols and bromoalcohols by elemental iodine and bromine, in the presence of some specific compounds such as Mn(II) salen complexes [23], 2-phenyl-2-(2-pyridyl)imidazolidine [24], thiourea [25] and diamines [26] as efficient catalysts. Among these catalysts, the Mn(II) salen complexes are more efficient and effective, but in this method, the oxidation of metal(II) in complex catalyst is an important limitation and reduced the activity of catalyst for next reusability. We would like to describe herein that H2TPP’s are highly reactive catalysts for the cleavage of epoxide rings to relative vicinal halohydrins in the presence of elemental iodine and bromine, more efficiently and regioselectively and in high yield under mild conditions that are highly desirable. The catalysts are easily recovered and can be reused several times. 2. Results and Discussion In this study, the reaction of styrene oxide with iodine and bromine in the presence of some derivatives of H2TPP as the catalyst were carried out (Scheme 1). Scheme 1. Catalytic conversion of epoxides to halohydrins. HO Y Y O Cat. (2a-e), r. t. + X2 R aprotic solvent R X 1a -h 3a -p N R of products Cat: N H H N 2a-e R of epoxides X=I X=Br N Ph a a i PhOCH2 b b j p-Cl-PhOCH2 c c k Y Y p-Me-PhOCH d d l 2 Y: H a t-Bu-OCH e m 2 e CH b n 3 3-Buten f f OMe c g g CH3 o i-pr d cyclohexene oxide h h p Cl e Molecules 2012, 17 5510 Derivatives of H2TPP and metal-TPP’s have been recognized as being among the most promising catalysts for various reactions [27,28]. These compounds show wide applicability and are now used as catalysts for a variety of regio and enantioselective reactions, such as CO2/epoxide coupling [29], acetolysis, hydrolysis and alcoholysis [30]. In all of these transformations, the coordinated metal ion in catalyst has a key role in the reaction process and this necessity causes some destruction of sensitive functional groups. After a solution of styrene oxide and a catalyst in CH2Cl2 was stirred in room temperature, a solution of elemental halogen in CH2Cl2 was added dropwise. The amount of the catalyst was a 0.05 molar amount of the styrene oxide used. The reaction product was 2-halo-1-phenylethanol (3a, 3i), and the yield was determined by GC analysis (Table 1). In each case, cleavage of the epoxide ring occurs and, upon thiosulphate workup, iodo- and bromoalcohol are obtained. The catalysts are easily recovered and can be reused several times. Tetraphenylporphyrin derivatives were prepared and metallated according to the literature [31,32]. Table 1. Addition of Iodine (1 mmol) and Bromine (1 mmol) to Styrene Oxide (1 mmol) in the Presence of Various Catalysts in CH2Cl2 at 25 °C. Iodination Bromination Entry Catalyst Time /h Yield a /% Time /h Yield a /% 1 2a 2.1 >95 1.7 >95 2 2b 2.1 90 1.7 >95 3 2c 2.2 87 1.8 90 4 2d 2.3 88 2.1 82 5 2e 2.5 76 2.0 75 6 b - Several days0 1 31 c a GC yield, based on epoxide; b In the presence of excess of halogen [29]; c The only one isomer, 2-bromo-2-phenyl-ethanol was formed. To ascertain the scope and limitation of the present reaction, a wide range of structurally diverse epoxides were subjected to cleavage by this method to produce the corresponding halohydrins. These results are summarized in Table 2. For comparison, a number of methods for the conversion of oxiranes to the corresponding halo alcohols are given in entries 10–14 (Table 2). However, other factors can exert a controlling influence such as: (1) steric hindrance of the epoxides (for example, compare in Table 2, entry 7 with entry 8); (2) the nature of the solvent; (3) the rate of admixing the reagents; and (4) the order in which the reagents are combined. Each one can have a pronounced effect on the observed ratio of -halohydrin isomers and the overall yield. The order and rate in which the reagents are combined were found to exert a subtle influence on the yield and regioselectivity in both bromohydrin and iodohydrin formation. However, if bromine is added to the epoxide before the catalyst, two isomeric bromoalcohols are produced, but if the epoxide is added to catalyst and then bromine is added dropwise over a period of time, only one isomer is formed. Furthermore, the rapid addition of bromine reduced the regioselectivity. Molecules 2012, 17 5511 Table 2. Reaction of various epoxides with elemental I2 and Br2 in the presence of catalyst 2a. Yield a Entry Epoxide (1a–h) Conditions Time/h Product (s) (3a–p) /% HO O 1 Ph I2, 2a, r.t., CH2Cl2 2.1 81 Ph I HO O PhO 80 3.9 ״ PhO 2 I OH O p-Cl-C6H4O 81 4.3 ״ p-Cl-C6H4O 3 I OH O p-Me-C6H4O 82 4.5 ״ p-Me-C6H4O 4 I I 78 6.5 ״ O 5 O HO O 82 4.6 ״ 6 I HO O O O 77 5.8 ״ 7 I O HO 72 3.5 ״ 9 I O b OO 10 Ph I2, r.t., acetone 2 83 Ph OH Br c [n-Bu4N]Br/Mg(NO3)2, 78 Br OH 5 ״ 11 CHCl3 (5:1) ph ph (Me N) BBr/CH Cl ,N 75 ״ 12 2 2 2 2 2 ״ d 12 atm. (1:4.5) I e SmI2 (2 eq.), min 93 OH 5< ״ 13 THF, −78 °C ph OH I f + − + 87 NH4 X /M ., CH3CN 1.3 I OH ״ 14 (1:2) ph ph HO Br2, 2a, r.t., CH2Cl2 1.7 91 ״ 15 Ph Br HO O PhO 84 2.0 ״ PhO 16 Br OH O p-Cl-C6H4O 82 2.4 ״ p-Cl-C H O 17 6 4 Br Molecules 2012, 17 5512 Table 2. Cont. Yield a Entry Epoxide (1a–h) Conditions Time/h Product (s) (3a–p) /% OH O p-Me-C6H4O 83 2.8 ״ p-Me-C6H4O 18 Br Br 80 2.7 ״ O 19 OH O O 76 2.5 ״ 20 Br HO O O O 78 3.5 ״ 21 Br O HO 73 2.2 ״ 22 Br a Isolated products yields based on epoxide; b Ref. [29]; c Ref. [17]; d Ref. [33]; e Ref.